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Venom Week Summary
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by Phobos on June 5, 2009
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Venom week 2009 summary
Basic science
There was quite a number of interesting basic science presentations given at venom week. I will discuss to very briefly.
Dr. Stephen P. Mackessy, professor of biology school of biological Sciences University of Northern Colorado. Dr. Mackessy describes some recent work regarding the structure of the venom gland in rattlesnake. The basic thesis was how the venom remains stable and not detrimental to the rattlesnake itself. He showed various a picture of the cellular structure of the venom gland and its accessory glands and drew the inclusion that rattlesnake venom glands are not that much different from a mix in the biological world. Stomachs produce digestive enzyme and have to protect themselves somehow from that digestive process itself. Snake venom glands seem to have a similar structure and accessory cells to that of a stomach. He also mentioned that the pH that venom in the gland is about 5.4 which is quite acidic. Most enzyme and proteins described in rattlesnake venom are quite an active at lower pH like the conditions found in venom glands. He theorizes that when venom is injected into prey tissues is immediately buffered to the pH greater than 7.0 and therefore becomes activated creating this syndrome we know as envenomation.
Dr. John Osterhout, chair of the Department of chemistry and biochemistry at Angelo State University San Angelo Texas. Osterhout described variation in venom composition in wild caught, captive animal and neonatal Crotalus atrox. He discussed the literature reports suggesting that venom from neonatal snakes of various species might be slightly more toxic in animal testing then adult this study indicates that the protein components and neonatal may might be sufficiently different from those in adult snakes and that complete neutralization may not be taking place with the antivenins available. This is why the urban legend of baby snakes being more topics or providing a worse by then adult snakes finds its credibility. He included that significant individual variations in the protein components of Crotalus atrox venom between wild caught captive adult and neonatal snakes were observed in a class the and neonatal venom were noticeably different from the two classes of adult venom he said, “the next logical step is to determine the specific venom components bound by antivenom
Antivenom science
Just as an introduction to the antivenom science discussion all of the medical doctors who specialize in treating envenomation said they could hardly think of a scenario where someone should use antivenom in the field or remote locations. Unless, there was qualified paramedic were physicians in the party with all drugs and tools required for resuscitation in the event of an adverse reaction to the serum.
An issue regarding the FDA approval of replacement antivenom for the Wyeth coral snake serum is still proceeding slowly. Wyeth is looking at testing old lots of antivenom to extend their expiration date as they did with the lot that's currently being used to treat bites.
Dr. Leslie Boyer medical director of the poison control Center in Tucson Arizona discussed the phase 2 trial results between CroFab and Bioclone AnaVip antivenom. This was actually a randomized comparative trial where the doctor and patient do not know which antivenom they were to receive. This study is a result the CroFab short persistence in a patient's bloodstream causing a later reading envenomation of the patient and when more venom fractions are circulating in the bloodstream. They three envenomation creates a rebound coagulopathy putting the patient again at risk from bleeding issues. The test was to see if Bioclone AnaVip was safe and effective and prevented this rebound envenomation. The conclusion was the pattern of rebound envenomation was not seen among patients treated with Bioclone AnaVip.
I would also like to note here that a physician who is quite respected in the area of snakebite treatment described CroFab as a poorly designed antivenom. This is something that most of us in the venom community realized years ago and is why Dr. Boyer and her colleagues in Tucson pursued the introduction of more effective antivenom. One more item of importance the Mexican developed and produced AnaVip seemed to be more effective on a wider range of snakes and costs much less.
Bioclone is also producing Pan African antivenom which is undergoing clinical trials in Africa. The early results look very promising.
Snakebite case presentation
There are many presentations of snakebite cases by the physicians who tended the patient. It's hard to describe how seriously ill some of these patients were and others less so without putting up actual charts of physiological data acquired during the treatment. Dr. Sean Bush describes two cases. One fellow received a Bibrons mole viper envenomation to the thumb. As everyone knew there was no specific or even para-specific antivenom available to treat the bite. The bite occurred in a state of California when the individual was bagging the specimen up then to Brian Fry in Australia. This fellow seems to find a loophole in the California law against keeping venomous creature except native specimens simply because the lawmakers didn't realize that some of the Family Atractaspididae (Stiletto Snakes, Mole Vipers) were venomous. Regardless this fellow was a hurting buckaroo who ended up having his thumb amputated. The surgeon doing the amputation said the whole end of the finger was just a bag of involved tissue and fluid being contained by the remains of the skin. Dr. Bush presented another case would seem to go well but then the patient had and ischemic stroke leaving him partially paralyzed this despite the fact that all of his blood coagulation value were within normal limits. All this from a Southern Pacific Rattlesnake bite, Crotalus Heller Dr. David Warrell theorize that the stroke was caused by components in the venom not neutralized by CroFab in which in turn activated protein in the endothelial cells that line vessels in the brain. The patient survived but did not regain complete function of the affected side.
Dr. Steve Curry of the Phoenix poison control center presented several cases involving bites by primarily Mojave rattlesnake, Crotalus scutellatus. This theory the bite he described were from the theory the bite that happened last summer that attracted media attention whining that the rattlesnake venom was changing and becoming more time to the human. This is a generally discarded theory because this can't occur just in the course of one or two summer but over thousands of years perhaps. Other possibilities why the venom were wreaking have it in people was that the snakes were directly injecting into the vein. This was only a good possibility in one case that Dr. Curry described where there was actual histological evidence of the fang track approaching a vessel in the surrounding tissue. In this case the woman bitten by the scutellatus was not found for a few hours allowing her condition to deteriorate. She had full blown disseminated intravascular coagulation upon arrival at the emergency department unlike most snakebite which has a DIC like presentation this was the real deal. She had major infarcts in major organs and did not survive the ordeal. Another patient bitten by what was described as the Mojave went through an uneventful clinical course and was about to be discharged when the doctor noted the patient with acting goofy. The doctor ordered in a CT scan and a subsequent MRI. The study showed the patient with multiple bleed throughout his brain. The patient survived but was unable to resume his normal life.
Those are just two of the many case studies presented at the conference no one is sure why so many bad bites are attributed to Mojave and Southern Pacific rattlesnakes. However, I can take the hint and will not have any of these bad boys in my collection.
These conferences all cause me to perform a gut check and consider my mortality. We choose to keep these dangerous animals and invite them into our homes. However, periodically it's good to take a step back and consider the possible outcome of ending up on the wrong side of one of these deadly snakes. A positive hospital outcome is not guaranteed there is still much that is not known about the venoms of these creatures and just how effective the antivenom are at neutralizing all of the components they inject. Another aspect to consider is the cost of the bite and who should bear the responsibility. Many of the envenomation that had positive outcome including a copperhead bite cost tens of thousands of dollars to treat. CroFab at a list price of $1500 per vial and many of the patients receiving 20 to 30 vials some receiving 50+ vials run up a very expensive tab very quickly. Hopefully the antivenin made by Bioclone (AnaVip) will solve some of these issues. We will have to wait and see.
Please note: all of the information here has been condensed by the author save time and space. However, the factual aspects have not been altered.
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RE: Venom Week Summary
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by Cro on June 5, 2009
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Al, thanks for posting the summary of the Venom Week Conference. It sounds like they covered a lot of important topics. Hopefully, the recognition that CroFab is not a very good product will help us get better antivenins available in this country.
Will printed transcripts of the conference become available?
I am especially interested in the study involving the pH of venoms. What immediatly comes to mind, is a possible first aid treatment involving injecting a acidic solution into the tissues that were bitten, thus possibly preventing the reaction of the venom with the alkaline body tissues. This could perhaps slow the action of the venom. Many acidic substances like ascorbic acid could possibly be used. This might be a research project that would be worth looking into.
And before anyone starts screaming that the venom spreads too rapidly, I am talking about a first aid measure that would have to be used within a minute following a bite, that could possibly be injected with a spring loaded syrynge, similar to a epi-pen. Anyway, just a stray thought for folks to think about.
Best Regards
John Z
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RE: Venom Week Summary
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by BobH on June 6, 2009
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Great summary Al and thanks for taking time to put it up here. Did they video tape this one? I got the complete set of the one a couple of years back. Your note on occasionally reassessing why we do what we do is well taken.
Bob
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RE: Venom Week Summary
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by Crotalusssp on June 6, 2009
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Thank you very much for the summary. I, like Bob, would be interested in a video if it becomes available. I think we should all stop more frequently to remember the possible consequences of an envenomation. Thanks again.
Charles
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RE: Venom Week Summary
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by JoeCrotalid on June 6, 2009
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Yes! The conference was taped and will become available on DVD within a few months after the editing process. Al did a wonderful job summarizing some of the highlights to the conference.
However! I believe he mistook some of the points about the lecture regarding CroFab vs. AntiVip. CroFab is effective for mild to moderate bites but does allow for reoccurrence, but has less affinity to causing allergic reactions. The AntiVip is of Equine origin and does allow more chance for analphylaxis. The point Leslie Boyer was attempting to make with her case study is the need for alternative antivenins. A sub-committee work group to the FDA advisory committee was started at the conference chaired by Leslie Boyer and which I was asked to serve on especially in light of the Coral snake antivenom situation to which I have been working on in Florida. The goal of the group is to #1 get the FDA to approve Coralmyn or the Costa Rican antivenin for use based on animal studies rather than waiting for actual human studies, and #2 to develop hospital based antivenom depots in various states for foreign antivenoms to ensure the exotic bites can be handled more rapidly.
The conference provides valuable information and contact resources to assist those of us who consult and treat these native and exotic bites. In addition, there are other companies considering developing additional antivenoms here in the states that was not made public, and I am not at liberty to Identify at this time.
Another issue this identifies though is the disclosure by private keepers of what they have in their collections so that these depots can obtain and stock antivenoms that cover those collections rather than stocking antivenoms that are not needed and wasting money. This a project I have tried to work on in the Tampa area for sometime but private collectors have refused to disclose a list of species for fear it would be made public which leads me to believe they are already doing something wrong since disclosure works to their benefit if bitten. It would mean the poison center would have already developed bite protocols to send to treating MD's and a list already written list of needed antivenins and their closest location to provide rapid treatment.
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RE: Venom Week Summary
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by JoeCrotalid on June 6, 2009
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Let me further something...the reason Leslie Boyer is pursuing BioClon AntiVip revolves around a case in which a patient was allergic to CroFab and despite multiple measures allergic reactions became more severe. They obtained AntiVip after a nightmare of issues including FDA regulations and logistical nightmares. Her point was the need to have multiple antivenoms for treament not that one was completely superior to another. As I said this had led to the Antivenom workgroup started at the conference.
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RE: Venom Week Summary
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by JoeCrotalid on June 6, 2009
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In addition Al...the reason AntiVip is currently less expensive is due to the fact that it is being used at a clinical trial site. CroFab at Sean Bush's hospital is only $500.00 a vial because it is a test site.
The same goes for an antivenom such as Coralmyn which cost $2000.00 a vial (Bioclon product). The cost is high because it is set by the distributor (in this case-Rare disease therapeutics). They will also be the distributor for AntiVip...so expect that cost to go up. In addition, the hospital will also add their cut into the cost. In the USA it's all about the almighty dollar.
The main point they were trying to make is that alternative antivenoms need to be readily available for use.
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RE: Venom Week Summary
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by Cro on June 6, 2009
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Joe, it is good to hear that a DVD will be made available from the conference. When you hear of that becoming available, please let us know here, as I am sure there are many who were not able to attend who would like to learn what was presented at the conference.
Also, it is good to know that the effort to make foreign antivenins available is continuing. Despite the dangers of the equine serum, it could possibly be better in treating many bites. The old equine based Wyeth product had a long track record of working if the allergic reaction could be prevented.
While we are on the subject, what ever happened to the folks who were going to use chicken eggs to develope antivenin ? That sounded like promising research. They had said that by using only the yolks, they though they could avoid most allergic reactions. Wonder is that research is still going on ?
Best Regards
John Z
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